title: Proteome variations in pancreatic stellate cells upon stimulation with proinflammatory factors.
abstract: Pancreatic stellate cells are key mediators in chronic pancreatitis and play a central role in the development of pancreatic fibrosis, stromal formation, and progression of pancreatic cancer. This study was aimed at investigating molecular changes at the level of the proteome that are associated with the activation of pancreatic stellate cells by proinflammatory factors, namely TNF-α, FGF2, IL6, and chemokine (C-C motif) ligand 4 (CCL4). They were added individually to cells growing in serum-free medium next to controls in medium supplemented with serum, thus containing a mixture of them all, or in serum-free medium alone. Variations were detected by means of a microarray of 810 antibodies targeting relevant proteins. All tested factors triggered increased proliferation and migration. Further analysis showed that TNF-α is the prime factor responsible for the activation of pancreatic stellate cells. CCL4 is associated with cellular neovascularization, whereas FGF2 and IL6 induction led to better cellular survival and decreased apoptotic activity of the stellate cells. The identified direct effects of individual cytokines on human pancreatic stellate cells provide new insights about their contribution to pancreatic cancer promotion.
authors.affiliation: From the Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Aseel J
authors.initials: AJ
authors.lastname: Marzoq
authors.affiliation: the Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Giese
authors.affiliation: From the Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Hoheisel
authors.affiliation: From the Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. Electronic address: m.alhamdani@dkfz.de.
authors.forename: Mohamed Saiel Saeed
authors.initials: MSS
authors.lastname: Alhamdani
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020543:Proteome
keywords: Antibody Microarray; Microarray; Pancreatic Cancer; Pancreatic Stellate Cell; Proteomics; Stromal Cell; Tumor Necrosis Factor (TNF)